Key Points:

• Prosigna and the Breast Cancer Index may be used in postmenopausal patients with breast cancer that is node-negative, ER-positive, and HER2-negative.
• Oncotype DX genomic test may be used in premenopausal patients with node-negative, ER-positive, and HER2-negative breast cancer.
• Premenopausal patients with 1 to 3 positive nodes derive a benefit from chemotherapy, regardless of the results of genomic assays.

A new ASCO guideline update provides further recommendations on the use of biomarkers to guide decision-making on adjuvant endocrine therapy and chemotherapy in patients with early-stage breast cancer.¹ The update includes clarification of the use of certain genomic tests, based on age or menopausal status, in patients with node-negative breast cancer and those with 1 to 3 positive nodes. The updated recommendations are based on new prospective randomized data and build on prior guidance published in 2016.²

Guideline Expert Panel co-chair Fabrice André, MD, PhD, of the Gustave Roussy, in France, noted that there have been several published randomized trials since the initial guidance in 2016, “and new concepts have appeared in this field, like the differential impact of genomic signatures according to menopausal status.”

In the 2016 guideline, the Expert Panel endorsed the use of several genomic tests to guide treatment decisions. These included the Oncotype DX, MammaPrint, Prosigna, EndoPredict, and Breast Cancer Index.² Following publication of data from the MINDACT and TAILORx trials, the panel released focused guideline updates for MammaPrint and Oncotype DX, respectively.^3-6 The most recent update addresses several new concepts and tools for early-stage breast cancer based on newly published randomized data.¹ These new data clarify the recommendations for biomarker use to include not only tumor characteristics, but also the patient's menopausal status or age.

New in 2022: Biomarkers in Node-negative, ER-positive, and HER2-negative Tumors

The updated guideline offers evidence-based recommendations for the optimal use of currently available biomarkers in patients with early-stage breast cancer who have tumors with known estrogen receptor (ER) and HER2 status.

For example, the guideline notes that Prosigna and the Breast Cancer Index may be used in postmenopausal patients with breast cancer that is node-negative, ER-positive, and HER2-negative. Additionally, the Oncotype DX genomic test may be used in premenopausal patients with node-negative, ER-positive, and HER2-negative breast cancer. The currently available data suggest that premenopausal patients with 1 to 3 positive nodes derive a benefit from chemotherapy, regardless of the results of genomic assays.

Further, the updated guideline endorses the use of Ki67, combined with additional parameters or the immunohistochemistry 4 score, to guide adjuvant treatment decisions in postmenopausal patients who lack access to genomic tests. In patients with 0 to 3 positive nodes who have received 5 years of endocrine therapy without evidence of recurrence, the updated guideline also recommends the use of the Breast Cancer Index to guide decisions regarding extended endocrine therapy.

How the Updated Guideline Informs Practice

“These and emerging data will allow for optimization of treatments to individual patients with early-stage breast cancer at the point of care,” said Vered Stearns, MD, FASCO, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, and guideline Expert Panel co-chair. “For example, if a genomic assay suggests that chemotherapy will not be helpful to an individual patient, optimization of treatment will allow for reduction in toxicity and cost of care.”

Dr. André added that the recommendations may have a “major impact because they contribute to inform one of the most frequent decisions in oncology: how to decide about a systemic treatment” in patients with early-stage breast cancer. “This decision must be taken in more than 1 million women each year worldwide,” he said, “meaning that [a] lack of evidence-based guidelines and [a] lack of education and dissemination could have a major impact.”

Research on Genomic Assays Still Needed

Dr. André noted that data on several important novel technologies are sparse, and additional research is needed to inform future updates to the guideline. For example, “the utility of circulating DNA should be better investigated in [the] near future,” Dr. André said. He also suggested that predicting the efficacy of anti–PD-1 antibodies in patients with triple-negative breast cancer will be more precise soon, and that data on this topic—if compelling—may be incorporated into future guidance.

According to Dr. Stearns, none of the markers addressed in the guideline have met the “threshold for use in women with triple-negative or HER2-positive breast cancer,” thereby limiting the generalizability of the recommendations across the broader breast cancer population.

“As new data become available, future updates will help us further refine genomic assay use based on tumor stage, tumor characteristics, and other factors, such as age or menopausal status,” Dr. Stearns said. “I hope that additional assays will become available to help guide use of agents in patients with triple-negative or HER2-positive breast cancer.”

Dr. Vered Stearns expects that “clinical assays will also be used to refine the incorporation of novel agents in the adjuvant setting, such as olaparib or immune checkpoint inhibitors.”

Dr. Stearns expects that “clinical assays will also be used to refine the incorporation of novel agents in the adjuvant setting, such as olaparib or immune checkpoint inhibitors.” In addition, she said that data are “urgently needed” regarding the performance of genomic assays in male patients with breast cancer, as well as in diverse communities, to develop clinical guidance for these populations.